Journal of molecular neuroscience : MN
-
The basolateral amygdala (BLA) is rich of CB1 cannabinoid receptors (CB1R) and has reciprocal connections with the nucleus accumbens (NAc) which is involved in opioid sensitization. In this study, effects of intra-BLA administration of CB1R agonist on sensitization to antinociceptive effect of morphine and changes in the levels of μ-opioid receptor (MOR), p-CREB, and c-fos in the NAc were investigated. Animals received intra-BLA microinjection of CB1R agonist (WIN55,212-2) once daily for 3 days consecutively (sensitization period). ⋯ The results indicated that intra-BLA injection of WIN55,212-2 during sensitization period resulted in the induction of antinociceptive responses by ineffective dose of morphine and caused a significant increase in the MOR and c-fos levels but not p-CREB/CREB ratio in the NAc. These finding revealed that CB1 receptor agonist in the BLA induces development of morphine sensitization and increases expression of MOR in the NAc. It seems that c-fos is one of the important factors involved in the induction of sensitization to antinociceptive effect of morphine.
-
Low CSF β-amyloid 1-42 has been associated with cognitive decline in advanced Parkinson's disease; data from a single cohort suggest β-amyloid 1-42 may be an early marker of cognitive impairment. Newly diagnosed Parkinson's participants (mean duration, 6.9 months) in the Parkinson's Progression Markers Initiative (n = 341) were assessed at baseline (untreated state) and followed for 2 years. CSF β-amyloid 1-42, α-synuclein, total tau, and tau phosphorylated at threonine 181 were collected at baseline. ⋯ Participants with CI at 2 years had significantly lower mean baseline CSF β-amyloid 1-42 levels than non-CI participants (343.8 vs. 380.4 pg/mL, p < 0.01); no significant difference was seen for α-synuclein, T-tau, or P-tau 181. In a regression model of 286 participants without baseline CI adjusted for age, gender, disease duration, education, motor severity, and depression status, lower baseline β-amyloid 1-42 levels were associated with higher odds of CI at 2 years. (OR(10pg/mL) = 1.04, 95 % CI 1.01-1.08, p < 0.05). CSF β-amyloid 1-42 level at disease onset is an independent predictor of cognitive impairment in early Parkinson's disease.
-
The aggregation of disease-specific misfolded proteins resulting in endoplasmic reticulum stress is associated with early pathological events in many neurodegenerative diseases, and apoptotic signaling is initiated when the stress goes beyond the maximum threshold level of endoplasmic reticulum stress sensors. All eukaryotic cells respond to the accumulation of unfolded proteins in the endoplasmic reticulum (ER) by signaling an adaptive pathway termed as unfolded protein response (UPR). ⋯ The UPR acts as a protective mechanism during endoplasmic reticulum stress, but persistent long-term stress triggers UPR-mediated apoptotic pathways ultimately leading to cell death. Here in this review, we will briefly summarize the molecular events of endoplasmic reticulum stress-associated UPR signaling pathways and their potential therapeutic role in neurodegenerative diseases.
-
Our previous studies demonstrated that propofol protects rat brain against focal cerebral ischemia. However, whether propofol attenuates early brain injury after subarachnoid hemorrhage in rats remains unknown until now. The present study was performed to evaluate the effect of propofol on early brain injury after subarachnoid hemorrhage in rats and further explore the potential mechanisms. ⋯ Furthermore, expression of Nrf2 in rat brain was upregulated by propofol, and expression of NF-κB p65, AQP4, COX-2, MMP-9, TNF-α, and IL-1β in rat brain were attenuated by propofol. Our results demonstrated that propofol improves neurological scores, reduces brain edema, blood-brain barrier (BBB) permeability, inflammatory reaction, and lipid peroxidation in rats of SAH. Propofol exerts neuroprotection against SAH-induced early brain injury, which might be associated with the inhibition of inflammation and lipid peroxidation.
-
Early exposure to sevoflurane, an inhalation anesthetic, induces neurodegeneration in the developing brain and subsequent long-term neurobehavioral abnormalities. Here, we investigated whether an enriched environment could mitigate neonatal sevoflurane exposure-induced long-term cognitive and synaptic plasticity impairments. Male C57BL/6 mice were exposed to 3 % sevoflurane 2 h daily for 3 days from postnatal day 6 (P6) to P8. ⋯ We found that sevoflurane-exposed mice housed in a standard environment exhibited a reduced freezing response in the contextual test, decreased number of dendritic spines on pyramidal neurons and synaptic plasticity-related proteins in the hippocampus, and impaired long-term potentiation. However, in an enriched environment, some of these abnormities induced by repeated sevoflurane exposure. In conclusion, neonatal sevoflurane exposure-induced cognitive and synaptic plasticity impairments are ameliorated by an enriched environment.